DIVERSITY OF CTL EPITOPES AND CHLAMYDIA

我们之前发现，能够特异性裂解衣原体感染细胞的细胞毒性T淋巴细胞（CTL）在沙眼衣原体感染期间被引发。将培养的 CTL 过继转移到受感染的小鼠体内可提供针对沙眼衣原体的保护。本提案中的实验使用生化方法来识别引起 CTL 反应的衣原体抗原。该提案中确定的抗原将使用重组炭疽毒素递送系统来测试其在疫苗策略中产生保护性免疫的能力。该项目将继续依赖其他核心和项目。还提出了初步实验，以解决在人类感染期间识别哪些抗原的问题。 我们设想这里描述的疫苗策略将被纳入旨在刺激免疫系统多个分支的多价疫苗中。开发有效的人类疫苗将减少这些感染的发生率，这些感染是造成全球大量发病的原因。这些实验不仅将进一步加深我们对 CTL 在衣原体免疫中的重要性的理解，而且还将提供对细胞内、液泡病原体的免疫识别的更好理解。 由于 MHC I 类分子上呈递的抗原通常存在于宿主细胞的细胞质中，因此鉴定逃离液泡区室并进行处理以在 MHC I 类分子上呈递给 CTL 的抗原子集将进一步了解这些非常复杂的宿主细胞-病原体相互作用。所鉴定的抗原类别也可能在其他细胞内液泡病原体中具有同源物，包括沙门氏菌、军团菌和分枝杆菌。

We have found previously that cytotoxic T-lymphocytes (CTL) capable of specific lysis of Chlamydia infected cells are primed during infection with C. trachomatis. Adoptive transfer of cultured CTL into an infected mouse affords protection against C. trachomatis. The experiments in this proposal use a biochemical approach to identify Chlamydia antigens which give rise to the response by CTL. The antigens identified in this proposal will be tested for their ability to engender protective immunity in a vaccine strategy using a recombinant anthrax toxin delivery system. This project will continue to rely on other cores and projects. Initial experiments are also proposed that will address which of these antigensare recognized during human infection. We envision that the vaccine strategy described here would be incorporated into a multivalent vaccine designed to stimulate multiple arms of the immune system. Development of an effective human vaccine would reduce the incidence these infections that are responsible for a great deal of worldwide morbidity. These experiments will not only further our understanding of the importance of CTL in immunity against Chlamydia, but also will provide better understanding of immune recognition by intracellular, vacuolar pathogens in general. Because antigens presented on MHC class I molecules generally are found in the cytoplasm of host cells, identification of a subset of antigens which escape the vacuolar compartment to be processed for presentation on MHC class I molecules to CTL will further our understanding of these very complex host cell-pathogen interactions. The class of antigens identified may also have homologues in other intracellular vacuolar pathogens including Salmonella, Legionella, and Mycobacterium.